Prosthetic valve and method of making a prosthetic valve

ABSTRACT

Prosthetic valves are provided with a leaflet assembly having at least one leaflet attached to a supporting element, which leaflet has a free margin that can move between a first position wherein the free margin is flexed away from a closure surface to allow body fluid to flow through the valve, and a second position wherein the free margin abuts the closure surface to close the valve, and wherein the leaflet, without pulsatile load on the valve, can form a coaptation height H of more than 0.1 mm along the length of the free margin. Such prosthetic valve provides good performance during prolonged time, and can be made using various materials for the leaflets.

CROSS-REFERENCE SECTION

This application is a continuation of commonly owned copending U.S. Ser.No. 15/857,359, filed Dec. 28, 2017, (now U.S. Pat. No. xx,xxx,xxx)which is a continuation of U.S. Ser. No. 15/308,981 filed Nov. 4, 2016(now U.S. Pat. No. 10,039,640), which is the national phase applicationof International Application No. PCT/EP2015/059982 filed May 6, 2015,which designated the U.S. and claims priority to EP Patent ApplicationNos. 14167271.7 filed May 6, 2014, 14167270.9 filed May 6, 2014,14167269.1 filed May 6, 2014, and 14167272.5 filed May 6, 2014, theentire contents of each of which are hereby incorporated by reference.

GENERAL FIELD OF THE INVENTION

The invention relates to implantable medical devices and methods ofmaking such medical devices, like a prosthetic valve and morespecifically a two- or three-leaflet prosthetic heart valve.

BACKGROUND

A typical natural valve of a mammal is the aortic valve, one of the fourheart valves. The aortic valve comprises three leaflets, also calledcusps, attached to the aortic root that serves as a supporting elementfor these leaflets. Each of the three leaflets of the aortic valve has afree margin and a margin where it is attached in semilunar fashion tothe aortic root. When the valve opens, the leaflets fall back into theirsinuses without the potential of occluding any coronary orifice. Thehingelines of adjacent leaflets meet at the level of the sinutubularjunction, forming at least part of the commissures. The body of aleaflet is pliable, extendable and thin to provide the requiredflexibility, although its thickness is not uniform. The leaflet isslightly thicker towards its free margin. On its ventricular surface isthe zone of apposition, known as the lunule, occupying the full widthalong the free margin and spanning approximately one-third of the depthof the leaflet. This is where the leaflet meets the adjacent leafletsduring valvular closure. With the valve in closed position, the marginsof the lunules coapt or meet together, separating blood in the leftventricular cavity of the heart from blood in the aorta. For a valve ofthis type, or a corresponding type, highest mechanical stresses duringopening and closing occur at the commissures and, to a lesser extent, atthe free margin of the leaflets.

Prosthetic valves are implanted in the human or animal body and may forinstance be used as a passive, one direction prosthetic valve within ornearby blood vessels. They can be completely preformed and implanted assuch, or formed in situ using the artificial and/or natural parts neededto form a functional prosthetic valve. A suitable prosthetic valve needsto open and close readily in response to differential pressure on eitherside of the valve, cause no or only little non-physiological turbulencein the blood flow, and avoid too much regurgitation. Cardiovascularproducts, such as heart valve prostheses, are thus subject to highrequirements with respect to loading conditions, both in magnitude as innumber of cycles. Typically, heart valve leaflets may undergo over abillion load cycles in their lifetime. Durability of prosthetic valves,especially of moving leaflets, is therefore an important requirement.

Any prosthetic valve should be able to resist the actual mechanical loadon the commissures and leaflet free margin during valvular operation andpreferably, maintain to resist such cyclical load during many years. Forthis, not only initial strength is an important parameter but alsoreducing the chances of (non-apparent) production anomalies in makingthe valve.

Today, valves used in valve surgery typically are bioprosthetic valveshaving leaflets made from biological tissue, often chemically treatedbovine pericardium. This is an elastic material that performs relativelywell and is able to mimic the natural valve. However, early failure isoften encountered, and is believed to be associated with high stresseson the leaflet material upon continuous stretching and retracting underpulsatile load. Various synthetic materials and designs have beenproposed as alternatives for making leaflets of prosthetic valves.

A valve prosthesis made using synthetic fibers is for example describedin NL1008349. This valve comprises a supporting element carrying anumber of leaflets, which have been made by winding reinforcing fibersonto a mandrel in specific directions corresponding to the occurringstresses in the leaflets. Since the fibers have to be positionedaccording to the maximum stress lines, this valve prosthesis isdifficult to make and uses many wound layers to accommodate stresses,whereby mass is added and flexibility may be compromised.

Similarly, U.S. Pat. No. 6,726,715 describes a leaflet for a heart valvecomprising a flexible sheet having stress-relieving fibrous elementsaligned with predetermined stress lines in the leaflet during valveoperation. Sheet material is typically PTFE or PVF, withhigh-strength/high-modulus fibers as reinforcing elements. Fibers suchas carbon, aramid, or polyethylene fibers like Dyneema® UHMWPE fibersmay be used.

WO2010/020660 describes making a prosthetic valve from for example auniform hollow braid made from polyolefin fibers. The hollow braid isshaped to form a valve by pulling it over a mould, comprising a tubularpart and a star-shaped part. By subsequently applying heat and pressure,the hollow braid takes the shape of the mould and different sections arecreated. Around the tubular part of the mould the braid forms into asection that corresponds to a supporting element of the valve, whereas astar shaped part of the mould provides a section that corresponds tomultiple valve leaflets. Before removing the valve from the mould, thefront and back sides of the valve prosthesis are edge trimmed. Toprevent disruption of the trimmed edge, the edge may be heat treated tomelt fuse the yarns to each other, provided with a stitching, orotherwise treated to make the edge mechanically stable.

Heim et al. in Materials and Manufacturing Processes, 26: 1303-1309,2011 disclose a method wherein artificial leaflets are made from wovenpolyester yarns by thermally shaping the woven textile on a mould into athree-cusp geometry; showing that woven polyester could be suited toform a valve prosthesis. Polyester yarn has stretching properties suchthat the woven textile is able to mimic the natural elastic stretchingof a human valve (about 15% of elongation), due to its typicalelongation at break of about 14-17%. In order to obtain a valve withgood contact between leaflets in closed position and to limit stressesduring working cycles, the authors teach to shape the leaflets such thatthere is a fairly large inherent opening in the centre of the valve,whereas under cardiac pulsatile load adequate coaptation is created overthe length of the free margin of the leaflets to prevent or at leastminimize regurgitation.

In US2008/0200977 an implantable valve prosthesis is described thatincludes a frame and at least one leaflet made from a syntheticbiocompatible polymer. The leaflet is designed such that its motion aidsin preventing blood stagnating in valve pockets, i.e. to preventthrombus formation. A leaflet is typically formed by casting a solutionof polymer, preferably segmented polyurethane, and by then providing twoslits to define a free portion that can unrestrictedly move in responseto fluid flow to open and closed positions.

A prosthetic heart valve comprising a valve body with multiple leafletsis disclosed in US2003/0114924, which is formed as a one piece bymoulding silicone or polyurethane. The valve is moulded to include a gapbetween the free margins of the leaflets in neutral position, and withleaflets having specific curvature along the free margin; such thatunder load of fluid flow the gap is closed and leaflet faces engage andform a coaptation area.

US2009/027039 describes an implantable prosthetic valve having at leastone leaflet and a restraining member for temporarily preventingsubstantial movement of the leaflet from open to closed position. Aleaflet may be made from various materials, like biological material orsynthetic polymers, but is preferably a thin metal film.

In US2005/0137681 a venous valve with a tubular frame and a cover isdisclosed, which cover includes surfaces defining a reversibly sealableopening and thus acting as leaflets. The leaflets can have various sizesand shapes, including arcuate edges, curved surfaces, a concavestructure, or include a curved support structure to efficiently closethe valve and restrict retrograde fluid flow. Leaflets may be made ofbiologic or synthetic fluid-impermeable material, including ePTFE, PET,urethane and polyethylene.

WO2000/62714 discloses a heart valve prosthesis including a one-piecemoulded body with a plurality of leaflets, made from a silicone orpolyurethane. In the neutral or rest position, the leaflets' freemargins converge to form a non-uniform gap therebetween. The leafletshave a scallop in their free margins, proving sufficient material at thecenter to seal against reversed fluid flow with minimum coaptation.

U.S. Pat. No. 4,191,218 discloses fabrics for use in vascular prosthesesand heart valves, which fabrics are woven from multi-filament(polyester) yarns comprising filaments of about 10 μm diameter, and areheat shrunk to result in open interstitial space of 20-40 μm andelongation in at least one direction of at least 10%. The fabricspreferably have a woven selvedge, which forms the free margin of a heartvalve leaflet.

US2012/0172978 describes a prosthetic valve comprising leaflets madefrom a filter screen material that has uniform pores of 15-60 μm and10-100 μm thickness, and is woven from e.g. polyester or polypropylenemonofilaments. In response to a closed flow pressure the leaflets can bepushed together to engage at the outflow edge, resulting in a coaptationof 3-9 mm. Methods of making such valve comprise forming separatelyleaflets from the screen material, coupling them together along anattachment line, and optionally coupling to a sewing ring orframe/stent.

In US2005/177227 a method of making a cardiac valve prosthesis isdisclosed, wherein a textile membrane, preferably made from polyester orPTFE, is shaped to form leaflets; for example by cutting out segmentsand using a shaped member reproducing the geometry of a cardiac valve inclosed artery position followed by thermofixation.

SUMMARY

The invention relates to a prosthetic valve (400) comprising a leafletassembly having at least one leaflet (3) attached to a supportingelement (2), which leaflet has a free margin (5) that can move between afirst position wherein the free margin is flexed away from a closuresurface (700) to allow body fluid to flow through the valve, and asecond position wherein the free margin abuts the closure surface toclose the valve, wherein the leaflet, without pulsatile load on thevalve, can form a coaptation height of more than 0.1 mm along the lengthof the free margin.

The invention is at least partly based on the recognition that knownprosthetic valves made from flexible sheet material, as in case of anatural valve, depend on substantial elongation (stretching) of thesheet material from which the leaflet is made, in order to providesufficient coaptation, that is contacting of the leaflet along its freemargin with the closure surface to close the valve, as well as toproperly open the valve during closing and opening cycles. Typicallyelongation has to be up to about 15% in order to provide sufficientcoaptation, in particular in the centre of the leaflet (which for asymmetrical cylindrical 3-leaflet configuration coincides with thecentre of the valve). This in its turn means that the sheet material hasto fulfil stringent mechanical property requirements in order to be ableand durably mimic the natural leaflet. Applicant realised that extensivestretching and durability, in particular in a natural environment, whichis immunogenic and may give rise to vegetation and other abnormalprocesses, are hard to combine. Based on this recognition, applicantdevised a prosthetic valve wherein also in neutral position, withoutpulsatile load on the valve, the leaflet is able to abut a closuresurface in the valve over a certain minimum coaptation height along itsfree margin. This coaptation height is contrary to prior art whereincoaptation is generally only created during actual pulsatile load on thevalve and thus depends on elongating the leaflet material and thedynamics of the process, rather than creating a valve that meets certainspatial restrictions per se. All-in-all, this means that the materialfrom which the leaflet is made has to meet less stringent demands onextendibility and thus, the current prosthetic valve and methods ofmaking it may provide at least more freedom in sheet material use, andprovides the option to make a more durable prosthetic valve. A furtheradvantage includes the possibility to use textile structures made fromhigh-strength, low-elongation biocompatible fibers, and thus use of thinflexible fabrics, preferably woven fabrics, for making prostheticvalves.

It is noted that the invention does not exclude that upon coaptation atsome point along the free margin, small channels or other openings cantemporarily be present for example due to the dynamics of the pulsatileprocess. The formation of wrinkles or other temporary imperfections inthe sheet material does not preclude the valve from proper functioning,as long as the leaflet has a geometry that intrinsically allows to closethe valve along the length of the free margin without pulsatile load,that is without requiring extension of the leaflet. Stated otherwise,the one or more leaflets have such geometry that without pulsatile loada certain minimum coaptation area is possible, such area defined by thecoaptation height and the length of free margin of a leaflet abuttingthe closure surface, thus preventing significant regurgitation in thevalve during actual use. Such geometry also results in sufficientcoaptation and effective valve closing with pulsatile load during use,even if the free margin itself would locally not fully abut the closuresurface.

The invention also relates to a leaflet assembly for use in a prostheticvalve, as further described herein. The invention further concernsmethods of making the prosthetic valve, including making the leafletassembly. More specifically the invention concerns a method of making aprosthetic valve comprising a at least one leaflet attached to asupporting element, which leaflet has a free margin that can movebetween a first position wherein the free margin is flexed away from aclosure surface of the valve to allow a body fluid to flow through thevalve, and a second position wherein the free margin abuts the closuresurface to close the valve, the method comprising

-   -   providing a sheet material, and    -   forming a leaflet assembly comprising at least one leaflet and a        supporting element from the sheet material,    -   wherein forming the leaflet assembly comprises shaping the        leaflet to impose a geometry wherein the leaflet, without        pulsatile load on the valve, can form a coaptation height of        more than 0.1 mm along the length of the free margin.

It is noted that “forming a leaflet assembly from the sheet material”may include steps such as folding, cutting, shaping the leaflet in amould, assembling multiple pieces of sheet material, connecting bystitching, gluing, etc. . . .

Definitions

A prosthetic valve is a constitution of at least one leaflet andsupporting element, wherein the leaflet is attached to the supportingelement such that the leaflet can flex or hinge to provide an open aswell as a closed position for the valve, and may optionally comprise arigid or semi-rigid support, also called frame or stent.

A leaflet assembly is the combination of at least one leaflet andcorresponding supporting element in a generally tubular configuration,and may be made from multiple pieces of material connected together orfrom one single textile structure (like a woven fabric). The leaflet isthe movable part and is attached to the supporting element, also calledgraft or skirt, and together they define pockets that can be filled withfluid to close the valve.

A commissure is generally a point or line along which two things arejoined; in anatomy of natural heart valves a commissure is the distinctarea of junction between two adjacent valve leaflets and theirsupporting vessel wall. Within the present application the commissurerefers to the attachment line or region from the outflow side between aleaflet and supporting element in case of a stent-less valve, andbetween leaflet and stent, and optionally supporting element for astented valve. In addition to connections forming a commissure, therecan be further connections between leaflet, supporting element and/orstent, for example further defining leaflet shape.

A margin of a leaflet is an edge.

Coaptation means abutting, contacting or meeting of a leaflet and aclosure surface, such as another leaflet, to close the valve; coaptationheight refers to the height or length of coaptation measured from thefree margin in longitudinal direction of the valve, i.e. towards thebottom of the leaflet.

The centre line of a leaflet is a hypothetical line from the free marginat the centre of the valve to the nadir at the bottom of the leaflet,that is the lowest point defining the leaflet by connections to thesupporting element. In case of a non-symmetrical valve with for examplethree leaflets, it is the line from the contacting or coaptation pointof the three free margins to the nadir.

The curvature height characterizes the curvature in the leaflet of avalve as the largest orthogonal distance between the centre line and astraight line connecting the free margin at the centre of the valve andthe nadir.

The radius of curvature of a leaflet is the radius of a circle that bestfits a normal section of the curved surface of the leaflet in closedvalve position.

An elastic material is a material that is capable of returning to itsoriginal shape after being deformed.

To impose a geometry on an object means that the geometry of this objectis established by the creation of the object, as opposed to a geometrythat can arise due to external forces applied to the object aftercreation.

Inflow side or bottom side of the valve means the side where fluidenters the valve when it is in open position, the opposite side isreferred to as outflow side or top of the valve.

For something to run parallel with another thing means that both thingspredominantly extend in the same direction.

The elongation at break of a specimen is the elongation of that specimenrecorded at the moment of rupture thereof under an applied load,expressed as a percentage of its original length. For sheet material,the elongation at break is often also called elongation at rupture orelongation at fracture.

A yarn is an elongated body having a length much greater than the widthof its cross-section, typically comprising a plurality of continuousand/or discontinuous filaments, said filaments being preferably alignedsubstantially parallel to each other.

Adjacent means adjoining or nearest in position.

A selvedge (or selvage) is an edge of a woven structure wherein thethreads that run in a direction perpendicular to the edge of thestructure are not extending from the structure as free ends, but arecontinuous at the edge by returning into the structure. Selvedges aretypically formed in fill (also called weft) threads during a shuttleweaving process, but may also be made with other techniques or in warpthreads.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1A-1I schematically show various steps for forming a valveprosthesis using a method according to the invention.

FIGS. 2A-2C schematically show various views of a textile structuresuitable for making a valve prosthesis according to the invention.

FIGS. 3A-3C schematically show the imposed geometry according to thepresent invention when compared to the prior art.

FIGS. 4A-4B schematically show various steps in a variant of the methodas described in conjunction with FIGS. 3A-3C.

FIG. 5 schematically shows how a selvedge can be woven in an edgeperpendicular to the warp direction.

FIGS. 6A-6F schematically show various steps in another embodiment of amethod according to the invention.

DETAILED DESCRIPTION

In a first embodiment the at least one leaflet of the prosthetic valveis formed to have such imposed geometry that—without pulsatileload—coaptation with a coaptation height of between 1 and 15 mm ispossible. It was found that such a height creates an adequate coaptationarea that effectively prevents regurgitation upon reversed fluid flow,while allowing fast and complete opening for fluid passage. Preferablythe leaflet geometry is made such that the coaptation height is at least2, 3, 4 or 5 mm and at most 15, 13, 11, 10, 9, 8, or 7 mm, for examplebetween 3 and 10 mm, preferably between 5 and 7 mm.

In another embodiment the geometry imposed to the leaflet comprises aconvex surface, relative to fluid entering at the bottom of the valve,having a radius of curvature at the centre line of the leaflet ofbetween 1 and 20 mm, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 or 20 mm, preferably about 12 mm. It isbelieved that an imposed convex geometry with this particular smallradius, as opposed to typical radii in known prosthetic valves of 50 mmor above, leads to less stress and deformation in the leaflet materialand possibly less tension on the commissures. Such geometry also resultsin pockets defined by leaflet and supporting element with relativelylarge volume, which will be filled with fluid during closing. This maybe advantageous for effective re-emptying upon opening, preventing e.g.blood remaining in a pocket and reducing risk of thrombus formation.

In still another embodiment the imposed geometry of the leafletcomprises a curved convex surface, wherein the curvature height of thiscurved surface at the centre line of the leaflet is more than 1 mm,preferably more than 2, 3 or 4 mm most preferably about 5 mm. A maximumvalue is inherently dependent on the outer dimensions of the valveitself, but is typically about 10-15 mm, for example 10, 11, 12, 13, 14,or 15 mm. It is believed that an imposed convex geometry with thisparticular shape, as opposed to typical heights between 0 and 1 mm forprior art valves, leads to less stress in the leaflet material andpossibly less tension on the commissures. It is noted that the curvatureof leaflet surface may be dependent on diameter of a valve, i.e. alarger diameter valve may have a correspondingly larger curvature.

In yet another embodiment the leaflet is formed such that the freemargin of the leaflet has excess length relative to the theoreticallength needed for closing the valve; for example relative to thedistance between the two ends of the free margin at the commissures viathe centre of the valve in case of a substantially cylindrical valvewith at least two leaflets. In order to create a preferred coaptationheight of at least 1 or at least 3 mm along the length of the freemargin of the leaflet, applicant found (contrary to the common design ofpericardium material like Carpentier-Edwards PERIMOUNT or textiledesigns like the design of Frederic Heim as described here above) thatit is advantageous to create excess free margin length. Such excesslength can be made in different ways. For example, in case of asubstantially cylindrical valve with radius R, and having three leafletsof same size that are attached to the supporting element with evendistribution between commissures the needed theoretical free marginlength would be 2 R. By making leaflets having at least the same size asthe supporting elements their free margin length would be at least 2πR/3; thus creating an oversize factor of at least about 1.05. Stillmore oversize can be obtained by designing leaflets and optionallysupporting elements to be larger relative to actual size of the valve orits stent during use. This can for example be done by reducing thediameter of a prosthetic valve comprising a stent and a leaflet assemblyof matching diameters by compressing the stent. It is noted thatUS2005/177227 describes a cylindrical valve with 3 leaflets, andindicates the length of the free margin of a leaflet to correspond totwice the length of the radius R, and thus to be less than thecorresponding segment at the periphery of 2 πR/3, in order to guaranteeclosure of the valve during diastolic phase. In general it was found tobe advantageous to make a valve wherein the leaflet free margins have atotal oversize or excess length factor of at least 1.07, preferably atleast 1.09, 1.11, 1.13 or 1.15, and preferably of at most about 1.4,more preferably at most 1.3, relative to the theoretical length neededfor closing the valve (for example relative to the minimum length neededto bridge the distance between commissures via the center of the valve).Stated otherwise, the free margins preferably have an excess length ofat least 7%, more preferably of at least 10 or 15%, and of at most 40 or30%.

In a further embodiment the excess length of a leaflet is created by oneor more of the method steps chosen from the group of preforming thesheet material to a specific shape, for example by forming atrapezium-like sheet material (i.e. a form wherein a section thatcorresponds to the leaflet forms the wider bottom half of the trapeziumand a section that corresponds to the supporting element forms thesmaller upper section of the sheet material), or forming a tapered orconical tubular material, reducing the outer circumference of the valve,for example by using a retaining ring or compressing a stented valve,and shifting the leaflet surface before final fixing of the leaflet inthe valve.

In still another embodiment a valve is made wherein the leaflet isattached to the supporting element along a commissure, which runs atleast for a certain length starting at the free margin in parallel withthe body fluid flow, that is parallel to the longitudinal axis of thevalve. This way the stress on the commissure is not concentrated at onepoint at the top edge, as in common designs, but is divided over saidlength, which may increase durability. In case the valve comprises arigid support or stent, the stent preferably has vertical posts to whichthe leaflet assembly is connected as part of forming a commissure,resulting in a stable and durable commissure. The commissure can runover the height of leaflet assembly or stent, but preferably has alength of 1-9 mm from the outflow side, or of 1-6 mm. It will be clearthat commissure length may be proportional to size (height) of thevalve.

In again another embodiment wherein the sheet material is an elasticmaterial, the sheet material has an elongation at break of 10% or less.It is an advantage of the present method, and completely against theteaching of prior art to use a material that allows elastic stretchingof about 15% or more (mimicking the stretch behaviour of natural leafletmaterial), that also a low-stretch sheet material, i.e. material thatcan be substantially less stretched and has substantially lowerelongation at break, can be used for forming a leaflet of a valveprosthesis. Less stretching during use is believed to provide moredurable leaflets and valves after implantation, not only from amechanical point of view but also since stretching an object may inducecollagen growing over this object. The low stretch characteristics ofpresent leaflets thus reduce or even minimize the impetus of potentialcollagen or connected tissue overgrowth, that would otherwise result inleaflet thickening and loss of mobility and possibly induce focalthrombi or other vegetation. In general, tissue overgrowth or fibrosismay lead to leaflet compaction, which will result in valvularincompetence. Preferably the elongation of the sheet material during itsuse in the valve made according to the invention is less than 9, 8, 7,6, 5, 4, 3, 2 or even 1%. The elongation at break of such sheetmaterial, occurring at higher load than during use as leaflet, issimilarly less than 9, 8, 7, 6, 5, 4, 3, 2 or even 1%. Without wishingto be bound to any theory, it is thought that imposing a leafletgeometry that also without load can provide a certain minimum coaptationheight, apparently allows a sheet material to be used that is low instretch or has a high mechanical resistance to stretching; that is asheet material with a high tensile modulus (also called Young'smodulus).

Although for example porcine intestinal submucosa (CorMatrix™) is anatural elastic sheet material that can be used for creating leaflets ina valve prosthesis (see for example Zaidi et al., doi:10.1016/j.jtcvs.2014.02.081), in an embodiment the sheet material is atextile structure comprising one or more elastic yarns having anelongation at break of 10% or less. As shown in some of the above citedpatent publications, a textile structure may also be suitable for makinga leaflet. Textile materials are easy to produce industrially on a largeand controllable scale. By using yarns that have an elongation at breakof less than 10%, preferably less than 9, 8, 7, 6 or 5%, preferablybetween 1 and 5%, the low stretch advantages as described here above canbe easily obtained. Textile structures or fabrics may be made withtechniques like knitting, braiding, or weaving.

In a further embodiment the textile structure is a woven fabric madefrom one or more threads or yarns. A woven structure has the advantageover for example a knitted or braided structure in that desired (non- orlow-) stretch properties and shape or form can be easily incorporated byapplying various weaving techniques, and by using various yarns as warpand fill (or weft) threads. Weaving pattern is not found to beparticularly critical, the skilled person will be able to select apattern in combination with selected threads to obtain desiredproperties with some experiments. Typically, woven fabrics with commonlyused patterns like plain, twill or basket weave patterns are found toprovide good performance.

One or more textile structures can be applied as sheet material forforming leaflets and a leaflet assembly. Suitable methods includeforming each leaflet and supporting element from a separate piece ofsheet material or textile structure and then connecting the variouspieces together; forming multiple leaflets from one textile structureand multiple supporting elements from a separate textile structure andthen connecting the two parts together; and forming multiple leafletsand supporting elements from a single textile structure into a leafletassembly. For example, a leaflet assembly having three leaflets andsupporting elements may thus be made from 6, 4, 2, or 1 piece(s) oftextile, preferably woven fabric. Suitable methods for forming a leafletassembly from a single woven fabric include applying double weavingtechniques that result in multilayer woven fabric, like a so-calleddouble width fabric that is open at one side, or a flattened tubularfabric; as will be further described below.

In a further embodiment the free margin of the leaflet is woven as aselvedge. A woven selvedge or simply selvedge (selvage in US English) isa self-finished edge of a woven textile structure. A selvedge refrainsthe textile structure from unraveling or fraying, but, as opposed toother types of stabilised or finished edges, a selvedge is the result ofthe actual weaving process, and not of an additional process step suchas cutting, melting, stitching or other process for providing astabilised edge. In a woven textile structure, selvedges typically (butnot necessarily) run parallel to the warp threads and are formed by thefill thread(s) looping back into the fabric around the last warp threadafter exiting. A selvedge is made inherently if fill threads aresupplied endlessly as in a shuttle weaving process, but can also be madein a shuttle-less weaving operation by tucking-in the fringed ends ofthe fill threads after each interlacing and cutting. A further method isintroducing additional threads with so-called leno selvedge design thatlock outermost thread ends at the edge of the fabric. By having thefree-margin woven as a selvedge, this free margin is provided as aninherently mechanically stable edge without using an additional processstep such as melting or stitching. Additional process steps maycomplicate the manufacturing process of the valve as a whole, and alsomay give rise to side effects, like alteration of mechanical propertiesof the yarns (such as for example increased stiffness, reducedresistance to wear or reduced strength) upon melt fusing of loose yarnends, or local thickening and reduced flexibility of the fabric afteredge stitching. Nevertheless, such additional edge finishing may besuitably used to stabilise edges of a woven fabric for use in making aprosthetic valve; for example in case of making a continuous or endlesswoven fabric that later is to be cut into desired lengths for forminge.g. leaflets. A suitable example of making a stabilised or finishededge is hot cutting of woven fabric, e.g. with a laser or with anelectronic thermal cutter, also called hot knife, which allowssimultaneously cutting and fusing fabrics of thermoplastic fibers in acontrolled single step. Alternatively, threads with leno design may beincluded during weaving of the fabric at the places where the fabric isto be cut.

In particular it has been found that it is advantageous to weave thetextile structure as a multilayer structure comprising stacked layers,which layers are preferably interconnected by crossing of warp or fillthreads at desired locations, or alternatively interconnected by sewingor stitching after weaving. Applicant recognized that by applying aweaving process wherein a woven textile structure is made that comprisesmultiple stacked layers—such process is commonly referred to as a“double weave” process and is typically used for making decorativefabrics-supporting element(s) and leaflet(s) can be formed in oneweaving process in the same textile structure, namely as differentlayers (or as sections in different layers) of such textile structure.At the same time leaflet and supporting element may attain a mutualconfiguration in the structure or subsequent leaflet assembly thatcorresponds to the mutual configuration the leaflet and supportingelement need to have in the ultimate valve, and also commissures may—atleast partly—be obtained as a direct result of the weaving process. Insuch multiple layer weaving, the longitudinal sides of layers can bemade as open edges, typically with a selvedge, or can be closed edges,by connecting two layers at their edges. Considering the size of a valvefor use in a bodily conduit like blood vessels or arteries, the width ofa textile structure for making a leaflet assembly will be on the orderof centimetres. Such size may appear relatively small for (industrial)woven fabric production, but suitable weaving methods, weaving patternsand machinery are known in the art for such purpose; for example thosegenerally referred to as narrow fabric weaving (systems) that aretypically used for making tapes and ribbons. In such weaving equipment,typically movement of every warp thread can be individually controlledto make multiple layers, and various connections between layers. Furtherinformation on such weavings methods is available on the internet, forexample on double weaving in the document available viahttp://www.cs.arizona.edu/patterns/weaving/webdocs/opr_rgdw.pdf.

In an embodiment a leaflet assembly is made from a single piece of aflat woven fabric, by folding to itself, forming into a tubularconfiguration by connecting the ends, and making further connectionsbetween the two layers to define leaflets and supporting elements.

In another embodiment a single woven textile structure is made by adouble weaving process resulting in a two-layer woven fabric, forexample a so-called double width fabric that has two selvedges at itsopen side, and a continuous fold line at the opposite closed side. Insuch structure one layer will form supporting elements and the otherlayer leaflets. The width of a layer is determined, for example, by thenumber of warp threads and warp thread dimension, and both layers can bemade to have the same or different width or size by varying therespective number of warp threads in each layer. In such weavingprocess, further connections can be made between the layers by crossingwarp and/or fill threads from one layer to another; this way for exampleat least partly defining a leaflet by a connecting line (which can be acommissure). The spatial arrangement of connecting lines will define theform and size of the leaflet and its free margin, and of thecorresponding supporting element. The leaflet can be made to have alarger size than the corresponding supporting element—to create excesslength of the free margin in the final valve—by (locally) increasing thenumber of fill threads in (the layer forming) the leaflet relative toits supporting element.

A woven fabric, including a double width fabric as described above, canbe made as a fabric of distinct length in a discontinuous process, as ona classical loom with warp threads attached to beams, but also in acontinuous weaving operation by continuously feeding warp threads to thewarp beam. In the latter case a continuous (or endless) fabric results,which can be cut into desired lengths. In both cases the obtained pieceof fabric can be made into a tubular structure by connecting the fabricedges with warp (or cut) ends together. A two layer woven fabric thenresults in a tubular structure, wherein supporting elements will formthe outside and leaflets are on the inside of the structure. The warpthreads in these embodiments run parallel to the free margin, which is aselvedge of the fabric (similarly for top edge of supporting elements).

In another embodiment, a woven textile structure is made by a doubleweaving process that results in a seamless tubular fabric, also calledflattened tubular fabric, flat-woven tubular fabric or hollow elongatefabric; as it results from a continuous fill thread crossing over fromone set of warp threads forming a first layer to the other set forminganother layer at each side edge after every interlacing. It is notedthat in such case an uneven total number of warp threads is used to omitweaving errors, typically referred to as ‘error corrected tubularweaving’ in the art.

In an alternative embodiment, a tubular woven fabric is made by using anendless warp beam, like a circular or triangular beam. Further, inaddition to a one tube or one channel structure, also multi-channel ormulti-layer tubular woven fabrics can be made by using multiple sets ofwarp threads and beams, specific designs of endless beams (that is beamshaving ends joined, like a circular loop), and/or specific crossingpatterns of threads between the layers or tubular structures.

As also described above, tubular fabrics can be made in a continuousweaving process or in a dis-continuous weaving operation. In anembodiment of the invention the method comprises continuous weaving, andthe resulting endless (multi-) tubular woven structure is subsequentlycut into desired lengths. One of the cut ends of the tube will form thefree margins of leaflets, but since warp threads running lengthwise inthe tube will after cutting extend from the fabric edge, a finishingstep to stabilize the cut end is applied. Various finishing methods canbe used for both ends of the tubular structure, preferably a thermaltreatment is applied to a woven fabric made from thermoplastic polymerfibers. More preferably cutting and finishing is combined by using a hotknife or other thermal cutting method. After finishing the cut edges,the tube may be partly inverted; i.e. part of the tube will form a tubewithin the tube and by making connections between the tubes the outsidewill form supporting elements and inside one or more valve leaflets.

In another embodiment a tubular woven fabric is made piece-by-piece by adis-continuous weaving process. This has the advantage that a selvedgecan be woven in the warp threads, by not connecting the warp threadsdirectly to the warp beam but via additional threads and/or hooks; forexample using the Pueblo-Navajo or warp selvedge system as known in theart.

In an exemplary embodiment a substantially cylindrical tube is made,ends are optionally stabilised, and subsequently the tube is partlyinverted to make a tube within the tube. The free margins of theleaflets will in this case be of substantially the same length as thecorresponding supporting elements; this way having an excess length ofabout 5%. In a further embodiment a tapered tube is made, preferably byusing a weaving process including gradual changes in number of warpthreads in the woven fabric as described in U.S. Pat. No. 5,800,514 orUS2014/0135906. A length of tubular fabric having a first diameter atone end that is larger, preferably at least 2 or 5% larger, than thesecond diameter at the opposite end and with a gradual transfer of firstto second diameter is provided, the ends are optionally stabilized. Thenthe tube is partly inverted such that the inner tube has a largerdiameter than the outer tube; meaning the free margins of the leafletswill have an excess length of more than 5%. Multilayer tubularstructures, as described further using drawings hereafter, can beprocessed in similar ways to form a leaflet assembly for use in themethod of the invention.

Preferably, a textile structure comprising one or more elastic yarnshaving an elongation at break of 10% or less is used as sheet materialfor making a leaflet assembly. In a further embodiment the elastic yarnhas a linear density of less than 120 dtex, preferably a linear densityof less than 100, 80, 60, 50, 40, 30, 20 or even 15 dtex, preferablylinear density of at least 5, 7, or 10 dtex; for example a lineardensity of between 5 and 30 dtex, or between 7 and 15 dtex. Applicantfound that there may be a major advantage in applying textile structuresmade from thin yarns for making a prosthetic valve (note: although dtexis not a parameter that denotes actual dimension or spatial length, inpractice it corresponds to yarn diameter since most synthetic andnatural materials for making yarns have a density of about 1 kg/dm³).Particularly, it was found that using such thin yarns in the textilestructure leads to a fabric that is very flexible, and thus enablingfast response of the leaflet under pulsatile load. The flexible leafletscan also easily align with the supporting elements, thus creating alarge effective orifice; and also induce less load on the commissure.Furthermore, it was found that the use of such thin yarns tends to leadto textile structures having relatively low pore size and lowpermeability, in particular in case of a woven structure. Combined withabove mentioned reduced risk of thrombus formation, this may contributeto good biocompatibility, high effectiveness, as well as durability ofthe valve.

Similarly, it was found to be advantageous that the thickness of singlelayers of the textile structure, preferably a woven fabric, ispreferably at most 200, 150, 120 or 100 μm and at least 20, 30, 40 or 50μm for optimal performance, for example between 40 to 150 μm, preferablya thickness of between 50 to 100 μm. In case of woven fabric, this layerthickness typically corresponds to a plain weave, basket weave or twillweave of (UHMWPE) filaments in warp and fill direction having a lineardensity of between 5 to 50 dtex.

In yet a further embodiment the textile structure compriseshigh-performance polymeric filaments, preferably having high tensilestrength or tenacity of at least 1 GPa and high tensile modulus of atleast 30 GPa. Examples include carbon fibers, aromatic polyamide fibers,aromatic polyester fibers, and ultra-high molecular weight polyolefinfibers. Preferably the textile structure comprises ultra-high molecularweight polyethylene (UHMWPE) fibers, more preferably the textilestructure comprises at least 80 mass % of UHMWPE filaments with atenacity of at least 2 GPa, more preferably the warp and/or the fillthreads substantially consist of UHMWPE filaments. Such multifilamentyarns have been found to be ideally suitable for use in woven fabric formaking leaflets and supporting elements of a valve prosthesis. TheUHMWPE yarns are durable, can be made with the desired mechanicalproperties and a medical grade is available commercially, which medicalgrade is hardly immunogenic. In particular, it is preferred to useUHMWPE yarn that has an intrinsic viscosity (IV) of at least 5 dl/g,preferably at least 10 dl/g, more preferably at least 15 dl/g.Preferably, the IV is at most 40 dl/g, more preferably at most 30 dl/g,even more preferably at most 25 or 20 dl/g. IV is determined accordingto method PTC-179 (Hercules Inc. Rev. Apr. 29, 1982) at 135° C. indecalin, the dissolution time being 16 hours, with DBPC as anti-oxidantin an amount of 2 g/l solution, by extrapolating the viscosity asmeasured at different concentrations to zero concentration. Particularlypreferred are gel-spun UHMWPE yarns, which typically have a Young'smodulus of at least 30 or 50 GPa. Preferably the UHMWPE yarn has atenacity of at least 1.2 GPa. Preferably the yarn used according to theinvention comprises at least 90 wt-% UHMWPE filaments and mostpreferably the yarn used according to the invention consists of UHMWPEfilaments, and has a Young's modulus of at least 50 GPa. A preferredexample of an UHMWPE yarn is Dyneema Purity® yarn obtainable from DSM,The Netherlands. This type of UHMWPE yarn is particularly preferred,being medical grade yarn available in low dtex versions, the yarnstypically having an elongation at break of around 2 to 4%. Tensilestrength (or strength) and tensile modulus (or modulus) of UHMWPE yarnare defined and determined at room temperature, i.e., about 20° C., onmultifilament yarn as specified in ASTM D885M, using a nominal gaugelength of the fibre of 500 mm, a crosshead speed of 50%/min and Instron2714 clamps, of type “Fibre Grip D5618C”. On the basis of the measuredstress-strain curve the modulus is determined as the gradient between0.3 and 1% strain. For calculation of the modulus and strength, thetensile forces measured are divided by the titre, as determined byweighing 10 metres of yarns; values in GPa are calculated assuming adensity of 0.97 g/cm³. The ultra-high molecular weight polyethylene maybe linear or branched, although preferably linear polyethylene is useddue to the very high tenacity and modulus obtainable by stretchingduring manufacturing of the yarn. Linear polyethylene is hereinunderstood to mean polyethylene with less than 1 side chain per 100carbon atoms, and preferably with less than 1 side chain per 300 carbonatoms; a side chain or branch generally containing at least 10 carbonatoms. The number of side chains in a UHMWPE sample is determined byFTIR on a 2 mm thick compression moulded film, by quantifying theabsorption at 1375 cm using a calibration curve based on NMRmeasurements (as in e.g. EP0269151).

In another embodiment, typically in case the sheet material is formedfrom semi-crystalline thermoplastic polymer, forming a leaflet assemblymay further comprise shaping the leaflet by contacting with a mould ofdesired shape, optionally heating the mould to a temperature of 3-60° C.(preferably 5-40° C.) below the melting point of the sheet material(i.e. the melting point of the polymer from which the sheet is made; seeISO11357-3 for a determination of the melting point of a polymer),optionally creep forming (i.e. altering its dimensions) the sheetmaterial, and submitting it to a controlled relaxation and/or plasticstretching to conform to at least a part of the mould. Such thermalforming process is for example described in WO2010/020660. With thisembodiment the geometry of the leaflet can be further fine-tuned, forexample to create certain curvature or to meet certain clinical demands.

In yet another embodiment, also typically in a situation wherein thesheet material is formed substantially from a semi-crystalline polymer,the method further comprises steps of decreasing the permeability of thesheet material by applying a coating or optionally arranging the sheetmaterial, preferably a textile structure, in a mould, heating to atemperature of 3-15° C. below the melting point of the polymer, andholding at a temperature of 3-15°C. below the melting point of thepolymer for 10 seconds to 2 hours to impart a partial connection betweenadjacent filaments and/or yarns in the textile. Depending a.o. on thecross section of the yarns and their arrangement in the textilestructure (for example type of weave), it can be advantageous todecrease the permeability of the textile structure. In this embodimentthe thermo-mechanical properties of the polymers of which the yarns aremade can be used to improve the permeability properties of the textilestructure.

In a further embodiment, the prosthetic valve further comprises a stent(also called rigid carrying structure or frame) and the method furthercomprises connecting the at least one leaflet and supporting element toa stent. Connecting may be done by using one or more connecting means,preferably connecting is done by applying stitches. Suitable stitcheshave such strength properties that a durable connection is obtainedunder the loading during use as prosthetic valve. Preferably stitchesare made by using a yarn or suture material that has similar strength asthe yarns in leaflets and supporting elements, more preferably by usingthe a yarn or a suture of suitable size or linear density, andcomprising at least 80 mass % of or made essentially from the same typeof yarn as in leaflets and supporting elements.

With regard to the use of a rigid carrying structure or stent, such astent typically comprises a rigid member, and often is of ring orcylindrical shape. Suitable materials for making a stent include rigidpolymers, fiber-reinforced polymers, metals and their alloys, ceramicsand combinations thereof. Suitable rigid polymers include polyacetals,dextroplast, polyurethane, polyethylene, polysulfones,polyethersulfones, polyarylsulfones, polyetheretherketones, andpolyetherimides. Suitable metals include biocompatible metals, such as,stainless steel, titanium, cobalt alloys, such as Elgiloy® , acobalt-chromium-nickel alloy, and MP35N, anickel-cobalt-chromium-molybdenum alloy, and Nitinol®, a nickel-titaniumalloy. In addition, stents can be produced from ceramic materials, suchas pyrolytic carbon, silicon carbides or metal carbides, hydroxyapatiteand alumina. Suitable stents can also be produced from carbons such asgraphite. Preferably, a stent is at least partly made from a superelastic alloy, or a shape memory alloy, such as Nitinol®, anickel-titanium alloy, that is available as a super elastic material, aswell as a shape memory alloy. Such a stent allows to easily insert thevalve prosthesis into the body in a desired position. Before insertion,the self-expandable stent is brought to a first (relatively low)temperature at which it has a compact configuration. This compactconfiguration allows to easily insert the stent (and the valve inconjunction therewith) into the body, using minimal invasive surgery.After positioning the stent, and due to the body temperature, the shapememory alloy will heat up and change phase, thereby changing its shape.For Nitinol® for instance, a phase change will occur between anaustenitic phase and a martensitic phase. As a result the stent willexpand and thereby create a clamping force against surrounding tissue.In another configuration, Nitinol® is super elastic and can beelastically deformed up to material strains of about 10%, thusdeformation of a valve towards a compact shape is possible, stillallowing elastic deployment to the final shape after placement.

The prosthetic valve made by the present method may be stent-less or maycontain a stent attached to the leaflet assembly. A stent-less valve orleaflet assembly may be also used as a valved graft or grafted valve;meaning that the supporting element layer thereof can be attached to thewall of a blood vessel or artery and function as a graft to (partly)replace or reinforce a weak or aneurismal vessel. In such embodiment theoutside of the leaflet assembly, the supporting elements layer, may befurther treated to reduce permeability, e.g. by providing a coating or afurther layer of material. A prosthetic valve with a stent provides someother advantages, for example the possibility of being implanted viaminimal invasive techniques using catheter systems. In an embodiment themethod thus further comprises attaching the leaflet assembly to a stent.

In another embodiment the prosthetic valve comprises two leaflets asdefined herein above, wherein the second leaflet acts as the closuresurface for the first leaflet and vice versa. The prosthetic valve mayalso comprise three leaflets, in which case each leaflet acts as theclosure surface for the other two leaflets.

The prosthetic valve as described herein can be used to replace a mammalvalve, like a human venous or a cardiac valve, via a surgical treatment;via classic operations or by minimal invasive and percutaneoustechniques, depending on the type of stent optionally used in theprosthetic valve.

In addition to the above described embodiments, the prosthetic valve andmethods of making such valve will now be further explained using anumber of schematic drawings, which are not necessary to scale, and maynot show all features or components for clarity reasons. Like referencenumbers in different figures refer to like features.

FIGS. 1 1A through 1L schematically show various steps of an embodimentof the method of forming a prosthetic valve. In FIG. 1A a loom 100 isdepicted, the loom having four warp beams (or loom bars) 101, 102, 103and 104. Warp yarns 10 are connected between the top two warp beams 101and 103, and between the bottom two beams 102 and 104. This way atextile structure having two stacked layers can be formed in one weavingprocess, using one loom set-up. For reasons of clarity, common otherparts of the loom, such as the heald frames (or harnesses) with heddlesto separate with a predetermined pattern warp yarns in one layer (or inboth layers) to form a clear space (or warp shed) through which (ashuttle or pick carrying) the fill (also called weft) yarn can pass, andthe optional bat (or reed) for pushing the fill yarn against the fell ofthe cloth, are not shown. Warp yarns may be attached to the beams(typical for a dis-continuous process), or may be continuously fed withbeams 101 and 102 as guiding members, and 103 and 104 in such caserepresenting a single fabric beam for receiving the two-layer fabricmade. The fill yarn 11 as shown in FIG. 1A is woven in the upper layer 3of the textile structure 1 by interlacing the fill yarn with the upperwarp yarns (e.g. forming a plain weave), and passes back at the edge 5of layer 3 towards fold line 12, where it is woven in the lower layer 2until it reaches edge 4 of this lower layer and passes back towards foldline 12. Note that for clarity the fold line is made to look larger inthe figure than in practice. This way, the edges 5 and 4 are formed asselvedges. The weaving process continues until the textile structure hasthe desired size. The result is a two layered woven textile structurecomprising a first distinct layer 2 having a selvedge 4, and a seconddistinct layer 3 having a selvedge 5. Layer 2 is connected to layer 3along the fold line 12, by having fill yarns passing from the one layerto the other. These layers 2 and 3 will form respectively supportingelement and leaflets of the ultimate valve, and the fold line 12 mayform a part of the connections between supporting element and leaflet.An alternate embodiment further includes interweaving of the layers 2and 3 by crossing yarns between layers other than at the fold line, toresult in further connections and forming e.g. more sections in a layer.

After the textile structure 1 is woven on the loom 100, it is releasedfrom the loom as is shown in FIG. 1B. It is now clear that the textilestructure is woven as a double weave (or double width) cloth, havingdistinct layers 2 and 3, each having a selvedge 4 and 5 respectively.The warp yarns 10 extend over a little length outside of the actualtextile structure at the non-selvedge edges. These edges may optionallybe stabilized, at this stage or later.

In a next step, as depicted in FIG. 1C, stitches 22 are added further(next to fold line 12) connecting the layers 3 and 2. By adding twolines of stitches 22 to this structure, layer 3 is divided in threeseparate sections corresponding to separate leaflets in the valve.

In a next step, as depicted in FIGS. 1D and 1E, the two non-selvedgeedges are brought together (i.e. the proximal end and distal end of thestructure are configured on top of each other), such that the textilestructure forms a tubular structure. As can be seen in FIGS. 1D and 1E,the leaflets of layer 3 are situated on the inside, while the supportingelements of layer 2 are situated on the outside of the structure. At theclosure 9 of the loop, the warp yarns 10 of both edges of the textilestructure meet. Subsequently, the closure 9 of the loop is processed tomake sure the closure can withstand the mechanical forces exerted on theprosthetic valve when in use. Firstly the loose warp ends may be cut andthen, as can be seen in FIG. 1E, the closure 9 is folded towards thesurface of layer 2 and thereafter secured with stitches 30.Alternatively, the folded ends are first rolled up and thereafter foldedagainst layer 2. This way, any loose warp yarns ends are no longerfreely exposed, but a disadvantage is that the rolled up closure 9 issomewhat thicker as compared to a non-rolled up closure. A furtheralternative is to stabilise the edges before stitching to layer 2.

In a another step, as depicted in FIG. 1F, an additional stitch 31 isadded, for example following a U-shaped line, which stitch furtherconnects sections of layer 3 and corresponding sections in layer 2, tobetter define the leaflets or make a 3D-like shape. A segment of thetubular structure showing one combination of supporting element andleaflet is shown in FIG. 1F. As can be seen, the free margin of theleaflet is formed by selvedge 5. The connections made comprise, startingfrom the free margin, stitch 22 and stitch 31. Stitches 22 and 31 canalso be continuous, i.e. stitches 22 may not extend over the full heightof the valve, but may deflect and continue forming the U-shaped curve ofstitches indicated as 31. This way, the leaflet and supporting elementtogether form a pocket. By taking a position adjacent the supportingelements, the leaflets may open the ultimate valve, and by taking aposition that extends away from the supporting elements, the leafletsmay close the ultimate valve.

Referring now to FIG. 1G, in order to even better shape the leaflet andpocket, a mold 37 may be used. Before stitching connecting line 31, mold37 may transpose the leaflet into shape, optionally by pulling theleaflet at edge 5 upwardly. This way, extra length is created betweenthe nadir and the centre of the valve along the leaflet. Another way ofcreating such extra length is to already weave a larger (sections in)layer 3 than in layer 2, by using more warp yarns in layer 3 than in 2.The steps as illustrated by FIGS. 1F and 1G can also be performed duringor after connecting to a stent.

Referring now to FIGS. 1H and 1I, the textile structure or leafletassembly made is connected to a circular wire stent 40 to make valve400. The leaflet assembly is placed within the stent and may be stitchedat its bottom to the stent with stitches 33, and at the top withstitching 32 connecting supporting elements 2. This stitching 32preferably continues to connect the leaflets and supporting elementswith the three stent posts 41 (see FIG. 1I), such connection furtherforming the final commissure. The free margins 5 of the three leafletsare also depicted in FIG. 1H. In this form, the valve 400 is closed bycoaptation of the leaflets in neutral position. Would the free margins 5be adjacent the supporting element 2 (i.e. adjacent the wall of stent40), the valve 400 would be open. Some more details of the stentconfiguration and its posts 41 are depicted in FIG. 1I. Knot 36 is madein suture 32, as connecting point for this suture aftercircumferentially connecting the fabric. In an alternative approach,stitches 33 may be made at this stage; than temporary connections 35 maybe used to keep the structure in place during suturing to posts 41, andcan be removed thereafter. FIG. 1I shows an alternate embodiment whereinthe leaflet assembly extends from the bottom of the stent, and this partmay in a further step be folded to the outside of the stent andconnected thereto. An advantage hereof may be smoother fitting to avessel or artery upon implantation.

In an alternative embodiment, instead of using stitches 22 early in theforming process (as shown in FIG. 1C), the double woven textilestructure as such (as shown in FIG. 1B) is tightly wrapped around thestent 40 (the stent at this stage being covered with a protective sheetof plastic) or another shaping member like a rod, and the four layers ofthe closure 9 are sutured together. Thereafter the stent is removedcarefully, and the tubular textile structure is placed inside the stent.Then, stitches (sutures) corresponding to stitches 31, 32 and 33 areprovided in order to form the leaflet cusps and secure the textilestructure to the stent.

FIGS. 2A, 2B and 2C schematically show various views of a textilestructure for making a prosthetic valve according to the invention. Inthe embodiment of FIG. 2A, across section parallel to the fill yarn ofthe textile structure 1 in the direction S, as shown in FIG. 1A, isgiven. As can be seen, the fill yarn 11 is interlaced in layers 2 and 3with warp yarns 10 to form a plain weave. By using the double weavemethod as depicted in FIG. 1, both layers 2 and 3 have longitudinal(i.e. parallel to the warp yarns) selvedges 4 and 5 respectively. Thefill yarn, at fold line 12 passes from layer 2 to layer 3 and viceversa, thereby forming part of the ultimate connections between leafletand supporting element. In FIG. 2B, a side view of this textilestructure in the direction V as indicated in FIG. 2A is given. In thisview, only the selvedges 4 and 5 are schematically depicted.

In an alternative embodiment, as depicted in FIG. 2C and representing asimilar viewpoint as in FIG. 2B, the fill yarn is interlaced with thewarp yarns in such way that cross lines 220 are formed in the textilestructure. The textile structure 1 now comprises in total 6 sections inthe two layers, viz. sections 2′, 2″ and 2′″ in the top layer andsections 3′, 3″ and 3′″ in the bottom layer. At the left cross line 220,the four sections 2′, 2″, 3′ and 3″ coincide along a line that willcorrespond to (part of) the commissure of the ultimate valve. For this,warp yarns pass from section 2′ to section 3″ and warp yarns pass fromsection 3′ to section 2″, as controlled during weaving by the movingpattern of heddles and warp yarns. This way not only a mutualconfiguration is obtained wherein each section corresponds with asupporting element or leaflet, but also, a leaflet-supporting elementconnection is formed as a direct result of the weaving process, and hassimilar strength as the fabric itself. This also means that less (oreven no) stitches need to be added to form the ultimate commissure,including attaching to a stent. A corresponding weaving process takesplace at the right hand cross line 220. By connecting the ends of thestructure obtained as depicted in FIG. 2C a tubular three-leafletstructure is obtained.

FIGS. 3A, 3B and 3C schematically show the imposed geometry according tothe present invention, and a geometry according to the prior art. Ineach of the schematic drawings cross sections through the central lineof a valve with two opposing leaflets 3 and 3′ are depicted in closed,but neutral position without load, which leaflets are attached to theirrespective supporting element 2 and 2′, in the depicted cross section atrespective nadirs 120 and 120′. Note that for a valve with threeleaflets the plane through the central line of one leaflet may have anangle of 60 degrees with the central plane of the opposite leaflet. FIG.3A shows the imposed geometry of two leaflets, without pulsatile load,when made e.g. according to the method of Heim (see Materials andManufacturing Processes reference as mentioned here above). At thecenter of the valve, there is a substantial gap G in neutral positionwithout load. This gap will close and further open under pulsatile loadby extending the leaflet material (about 15%, partly due to stretch ofthe polyester yarns, partly due to a rearrangement of the yarns in thetextile), mimicking the dynamics of a natural valve. The radius ofcurvature of the leaflets is around 50 mm without pulsatile load.

FIG. 3B shows a cross section of a leaflet assembly in a prostheticvalve according to the invention. The opposing leaflets 3 and 3′ have animposed geometry in neutral position without pulsatile load that makesthem abut each other along the length of the free margin, thus also atthe centre of the valve, and therewith form a coaptation 700 with acoaptation height H at this cross section. The coaptation height H inthis embodiment is 6 mm at the centre and extends with a minimum of 0.1mm (the bottom of which is indicated with reference number 300) over thelength of the free margin of each of the leaflets, possibly being evenlarger towards the commissures depending on commissure length. Thegeometry also comprises per leaflet a convex surface that extendsbetween the top of the closure surface H and the respective connectionsto supporting elements, of which nadirs 120 and 120′ are shown in thecross section of the valve in FIG. 3B. Each convex surface bulges awayfrom the respective supporting elements 2 and 2′.

In FIG. 3C it is shown that by a slight hydrostatic pressure, created byfilling the pockets with water 600 as indicated, the imposed geometryand the coaptation height including formation of a closure “ribbon”having the length of the free margins can be inspected more easily andits dimensions estimated. It is noted that due to excess length of thefree margin (more textile length then actually needed to span thedistance between supporting elements and to coapt), it might be that atsome spots when closing the valve by filling it with water, there is awrinkle or small opening (a channel) in the closure surface. Suchopening however is not persistent and will be closed in actual use bypulsatile. The curvature of a leaflet may also be characterized by acurvature height h, defined as the largest orthogonal distance betweenthe centre line and a straight line connecting the free margin at thecentre of the valve and the nadir.

FIGS. 4A and 4B schematically show a continuous structure producedaccording to another embodiment, in line with the method as described inconjunction with FIG. 2C. In this embodiment a textile structure 1 iswoven with two fill yarns, one for each layer, so that the top andbottom layers 2 and 3 have a selvedge at both sides (4, 4′, 5 and 5′).Layer 2 is larger in width direction than layer 3 by using more warpyarns; note that only at the edges warp yarns 10 are depicted for bothlayers. In the resulting leaflet assembly the supporting element willthus be longer and extend away from the leaflets; and thus can be usedfor example to fold around a stent. The selvedges 5 or 5′ may form thefree margin of the leaflets in the resulting valve. In an alternativeembodiment, the extending supporting element layer can be used to attachthe leaflet assembly to the wall of a vessel or artery, thus functioningas a graft to (partly) replace or reinforce a weak or aneurysmal vessel.Such leaflet assembly, also without a stent, can thus function as avalve and as a graft, and may be called a valved graft or grafted valve.In such embodiment the outside of the leaflet assembly, the supportingelements layer, may be further treated to reduce permeability, e.g. byproviding a coating or a further layer of material.

The bottom layer is extended with extra fill yarns to increase the sizeof the (free margin of the) leaflet. When the desired extra length forthe leaflets is reached, layer 3 is pulled back with retaining bar 105so that the fill line of the top layer is in line with the bottom layeras shown in FIG. 4A. The warp yarns of the bottom layer and thecorresponding part of the warp yarns of the top layer are than crossedto form cross line 220; also shown in FIG. 4B. These cross lines providethat a commissure at least for the length formed by cross lines 220,starting at the free margin runs in parallel with the longitudinal axisin the ultimate valve formed out of structure 1 (corresponding to themethod as outlined in FIG. 1). After weaving, the product may be cutinto desired lengths, and connected to form a tubular structure, andoptionally connected to a stent.

Alternatively, leaflets may be made to be larger than supportingelements. In a further alternative way, a fold line is formed at oneedge by crossing fill yarn to the other set of warp yarns.

FIG. 5 schematically shows how a selvedge can be woven, even in an edgeperpendicular to the warp direction WA. In this case, connected to thewarp beam 101 is a stay, comprising multiple hooks 62. The warp yarns 10each form a loop, and each of these loops is connected to the beam usingthe hooks of the stay, which thus extends between the warp beam 101 andthe said loops. The fill yarn 11 is interlaced with the warp yarns 10 infill direction WE. In this particular embodiment a cord 60 is used tofix the said loops to the hooks 62. For this, the cord 60 extends alongthe margin 13 through each loop of the warp yarns, and is connected tothe warp beam using the stay as indicated here above. In this case, thecord 60 is a section of a warp yarn and further continues as the fillyarn 11, so no loose ends are adjacent edge 13. Using this method thewarp yarns at the margin 13 form a loop, and thus are continuous at thismargin, which is thus formed as a selvedge. The selvedge in this caseextends in the fill direction WE, perpendicular to the warp directionWA. The resulting flat fabric has thus at least selvedges at three ofits edges. This way of forming a selvedge in warp threads can alsosuitably be used in forming non-flat but e.g. tubular textilestructures, wherein this edge or margin corresponds to the free marginof the leaflet of the ultimate valve. Examples of such tubular textilestructures are schematically depicted in the following figures.

In another embodiment, the hooks connect the warp beam directly to loopsof the warp yarns. To prevent a free end of the fill yarn, it ispreferred to loop the fill yarn around one of the warp yarns(advantageously a yarn near a side of the weave if the weave is a flatweave) and thereafter weave using the two ends of the fill yarn asindividual fill yarns.

It was found that use of UHMWPE yarns as fill yarn was particularlyadvantageous when preparing a woven fabric with a selvedge parallel tothe fill yarns as the yarns tended to adjust transversely, to fill theloops of the warp yarn when stay or hooks were removed. It could betheorized (without wishing to be limited thereto) that this surprisingfinding for a yarn with very high strength and modulus, is related tothe combination of the low friction coefficient of UHMWPE and bendingflexibility of UHMWPE yarns.

FIGS. 6A through 6F schematically show various steps in anotherembodiment, in which method a tubular (endless) woven textile structureis used for making a leaflet assembly for a valve.

FIG. 6A (warp direction is indicated as “WA”, fill direction as “WE”)shows a woven tube-like textile structure 1 consisting of inner tubularlayer 2, corresponding to the supporting elements of the ultimate valveas depicted in FIG. 6E, and outer layer 3 having three sections, whichwill correspond to leaflets having excess length in the free margins.The outer and inner layer are connected along three lines 220. In thisembodiment the inner tubular layer 2 has selvedges 4 and the layer 3 hasselvedges 5, a textile structure resulting from e.g. the methoddescribed in FIG. 5 using a warp beam of specific design. Alternatively,such structure is made in a continuous weaving process, followed bycutting to desired lengths and making stabilised edges. The leafletsections in layer 3 are connected to the supporting elements in layer 2via cross lines 220 (corresponding to cross lines 220 as depicted inFIG. 2C, albeit that in this case the fill yarns cross, whereas in FIG.2C the warp yarns cross).

FIG. 6B gives a top view (or cross sectional view) of the textilestructure of FIG. 6A (in warp direction). FIG. 6C gives the same view,but with the textile structure from its original flattened form nowbeing configured such that layer 2 forms a circular tube. The leafletsections of layer 3 extend over the surface of this tube and meet at thecross lines 220. In a next process step the textile structure of FIG. 6Cis turned inside out, which leads to a structure as depicted in FIG. 6D.At this stage, the textile structure is processed such that thesupporting elements 2 are on the outside, and the leaflets 3 are on theinside, thus forming a leaflet assembly or valve 400 as shown in FIG. 6Ein an isometric view (in closed valve configuration).

In FIG. 6F an alternative embodiment of a textile structure using amethod similar to that described above is schematically depicted, inwhich embodiment layer 2, unlike the structure as shown in FIG. 6A,extends over a longer distance than the layer 3. In this embodiment, themargin 5 of the leaflet section(s) in layer 3 is formed as a selvedge(for example using a circular warp beam and using a method as depictedin FIG. 5), and the margin of layer 2 is woven as a regular edge whereinthe warp yarns are discontinuous at the edge (for example discontinuoussince they are cut to release the structure from the loom). Forsimplicity only some ends of warp yarns 10 are depicted, similarly toFIG. 6A. This textile structure can be formed into a valve the same wayas the structure of FIG. 6A, that is by inverting. An advantage of theresulting leaflet assembly is that the supporting element is longer,extending away from the actual leaflets, and thus can be used forexample to connect to the outside of a stent used in making a prostheticvalve or to attach the leaflet assembly to an artery as a valved graft.Similarly layer 2 may extend at the opposite end of the structure, orlayer 3 may be made larger.

The invention will be further elucidated by the below exemplaryexperiments.

EXAMPLE 1

This example describes making a prosthetic valve according to theinvention, and experiments wherein such valve is tested in vitro andused as a pulmonary valve prosthesis by implanting in sheep. In thisexample, each valve is made with the method described below, which isbasically corresponding to the method as described in connection withFIG. 1 and FIG. 3B.

A woven fabric as shown in FIG. 1B was made from Dyneema Purity® TG 10dtex UHMWPE multifilament yarn (available from DSM, The Netherlands)with a density of 458 warp yarns per inch and 223 fill yarns per inch.The folded two-layer structure had a length of 90 mm and a width of 21.5mm, a layer thickness of 0.00314 inches (80 μm), and was woven as a 2 by2 twill weave, with longitudinal selvedges. The cylindrical stent usedhas the design as shown in FIG. 1I, and was made of electromagneticallypolished stainless steel 304. It had an outer diameter of 25 mm, aninner diameter of 23 mm and a height of 17 mm. For the stitches, twokinds of suture thread was used: Maxbraid PE 3-0 suture blue withtapered needles (available as MPC 900252 from BIOMET MERCK LTD), herebeneath referred to as Suture A, and Maxbraid PE 4-0 suture blue withtapered needles (available as MPC 900244 from the same supplier), herebeneath referred to as Suture B. Both sutures comprise UHMWPE yarn.

The pulmonary valve was made as follows. In order to create a coaptationheight of 6 mm over the length of the free margins of the leaflets,extensive free margin length was created. The free margin length wasoversized by following steps:

-   -   1. The leaflet free margin length in the textile structure as        woven will be inherently equal to the supporting element length,        the two layers having the same length. The distance between the        edge of the supporting element formed as a cylinder and the        middle of the valve being its radius R, the total length needed        for 3 leaflets bridging this distance is 6 R, whereas the length        of the supporting element is 2 πR. This creates an inherent        excess length factor for the leaflet of 2 πR/6 R=1.05.    -   2. The two layer woven fabric is initially wrapped around (i.e.        to the outside of) the 25 mm stent and the ends perpendicular to        the free margin of the leaflets are sutured together.        Subsequently the cylindrical textile structure is placed inside        the stent of inner diameter 23 mm and fixed to the stent with        UHMWPE sutures. This creates an excess length factor of        25/23=1.09.    -   3. In this example the final prosthetic heart valve size is 23        mm for implantation, therefore the stent of 25 mm outer diameter        is radially compressed to 23 mm. This way the inside diameter of        the stent where the supporting element and leaflet is fixed to        is reduced from 23 mm to 21 mm. This creates an excess length        factor of 23/21=1.10.

The total excess length factor of leaflet free margins created this wayis π×25/3×21=1.25. The excess length thus created is about 25%.

As indicated here above, the woven fabric is tightly wrapped around thestent, initially being used as mold, and the four layers at the closure(corresponding to 9 in FIG. 1D) are sutured together with Suture Astarting at the outflow side of the fabric/stent combination by creatinga knot 36, leaving about 2 cm loose end and a long end which is used tocreate a stitch line towards the inlet side of the fabric/valvecombination. The stent/mold is removed carefully, and the tubulartextile structure is placed inside the stent. The orientation of thewarps of the leaflets and supporting element are perpendicular to thelongitudinal central axis of the stent and commissural stent posts, ergothe fill yarns are in parallel to the central axis and commissural stentposts. The Suture A is then guided across fringe and stent post holesfrom inlet side towards outlet side (as shown in FIG. 1I), thus fixingthe stent post 41 to the supporting element and leaflet at a length ofabout 9 mm. At the top of the post (outflow side) suture A is used tofix the edge of the supporting element to the stent in a continuous wayby taking locked bites at the bended ends of the stent (the commonlyknown “Method of Blalock” using a festooning suture line). The end ofthe suture A is tied to its beginning at knot's 36 loose end. Thetextile structure is temporarily fixed to the remaining commissuralstent posts 41 in a 120 degree fashion thus dividing it in three partswith about the same free margin length, to keep the structure in placeduring next steps; after which the temporary fixations can be removed.

A second suture B is used to complete attaching of the textile structureand create the actual leaflet assembly within the stent, by stitching tothe two remaining stent posts 41 with a length of about 9 mm, and bystitching leaflet layer to the supporting element layer and stent tocreate the valve cusps. Prior to suturing, the free margin of all threeindividual leaflets were pulled up 3 mm in the middle of the free marginat the expense of length of the supporting element at the inflow sidethus creating an arch of woven fabric between commissural posts elevatedover the plane of the stent outflow side. Together with theaforementioned excess length this results in about 6 mm coaptationheight in the center of the heart valve, and is likely even highertowards the commissures of about 9 mm. A mold (a negative form takenfrom a human aortic valve) is used for further sizing and shaping thebelly of the leaflet as shown in FIG. 1G. The leaflet assembly istemporarily sutured (35) in the middle between the posts at the inflowside to maintain this configuration during next step. From this pointsuturing is started according to FIG. 1I. At the top of the post theleaflet and supporting element are taken double with two encirclingbites. The leaflet sheet is pulled a little bit backwards over the topof the stent and is fixed by the suture. The course of the suture lineof the leaflets (U-shaped) is also guided by the shapes of the stent andmold. The end of the suture is tied to the loose end left at the knot ofthe beginning of suture B. The resulting leaflets had a convex surfaceat the centre line of these leaflets with a radius of curvature of about12 mm without pulsatile load. This was estimated to represent a distanceh as depicted in FIG. 3C along the centre line with a height h of about5 mm. The textile structure extends a few millimetre from the stent atthe inflow site, as also shown in FIG. 4I, which can be used to attachthe valve to vessel or artery wall upon implantation. The leafletassembly is further connected with sutures to the lower part of thestent, and the temporary sutures 35 are removed.

After this fixation of leaflet assembly, the stent 40 of the valve iscompressed from 25 mm diameter to 23 mm diameter and sterilized by usingethylenoxide sterilization.

Performance of valves made as described above was tested both in vitroand in vivo. Mechanical and functional testing of the prosthetic heartvalve was performed in a simplified mock circulation. A BVS 5000circulatory assist device (Abiomed, Danvers, Mass., USA) was included ina closed loop circuit having a reservoir and a return conduit. The heartpump bladder was driven by an Intra Aortic Balloon Pump (Maquet,Rastatt, Deutschland) with a frequency of 80 beats/min and output of3600 cc/min, while afterload at the outflow side of the heart pump wasset to 80 mmHg using a water column. In an initial test the standardvalve of the heart pump at the outflow side was replaced by a valveconstructed with three single leaflets made from woven fabric of 55 dtexUHMWPE yarn mounted in a transparent plastic conduit to study its openand closure behavior. This pilot valve sustained >4 weeks (3.571.200cycles) while competent without deterioration of the woven leaflets.Build on this experience, a valve constructed as above (based onleaflets from woven fabric of 10dtex UHMWPE yarn), was tested underequivalent physiologic loading conditions of the systemic humancirculation, cumulatively during over 120 days (13.824.000 cycles). Thevalve opened fully into an optimal effective orifice, having commonlyknown vertical position of vibrating leaflets in parallel to the fluidstream, and closed while visually not revealing closure defects alongthe coaptation line of meeting free margins of leaflets, except from atiny central hole of about 0.5 mm. Visual inspection after testingrevealed a completely intact valve geometry; leaflets showing no frayingat the free margin or any other disruption or defects. All the suturelines as described above, as well as the knots were intact.

The prosthetic pulmonary valves were also implanted in adult sheepmodels (bread “swifter”, body mass 55-70 kg) on the beating heart, whileusing an extra-corporeal circulation machine. Access to the pulmonaryartery was achieved through left thoracotomy 3rd-4th i.c.s. Thepulmonary artery was incised longitudinally, whereafter the nativeleaflets were cut out. Three positioning stitches of 5-0 Prolene® wereused to pull on the commissural native posts. The valve was sutured intothe pulmonary artery on the supra annular level (plane top of nativecommissures) using 5-0 Prolene®. The pulmonary artery was closed inlinear fashion.

Echocardiography showed normal leaflet function without valvular orparavalvular regurgitation, apart from some occasional minimalregurgitation in the centre of the valve. The wound was closed and thesheep was taken to stables for recovery.

The sheep remained stable, without any adverse clinical signs up to 6months observation periods. After this period the leaflet function wasassessed again. Echocardiography showed adequate leaflet function withminor to moderate valvular but no paravalvular regurgitation, and therewas no change in effective orifice since the day of implant. After this,the valves were taken out of the sheep for inspection. The leaflets andsupporting elements were overgrown with tissue, but this appeared to bea very thin layer of fibroblasts and endothelial cells withouthistological and radiological signs of tissue calcification, and with amaximum thickness (including the leaflet) of 250 μm at the free edgewith increasing amount of streamlining repair tissue towards the nadir.The mechanics of the valve appeared to be unaltered, all sutures were inplace without fractures and the free margin of the leaflets appeared tobe completely intact as originally made. No signs of fraying or otheranomalies could be detected. The inventors are not aware of otherstudies using a prosthetic valve having leaflets made from a fabricwoven from synthetic fibers, and wherein animals having such implantedvalve survived a 6 months period without complications.

EXAMPLE 2

A prosthetic aortic valve to be implanted in the systemic circulationwas made analogously to Example 1 with some modifications. Thesupporting element was prepared by taking out three half-moon pieces offabric (facing the sinus valsalva in the human or animal aorta) to allowblood supply to flow into the coronary ostia. The remaining edge of thesupporting element was fixed to the leaftlet according to correspondingsuture line of the U-shaped cusp suture line (facing the sinusvalsalva). A second suture was used to complete attaching of the textilestructure and create the actual leaflet assembly within the stent, bystitching to the stent posts 41 with a length of about 9 mm, and bystitching the leaflet layer to the supporting element layer and stent tocreate the valve cusps.

The valve was subsequently constructed in similar way as the pulmonaryvalve described here above. When completed, an additional sewing cuff ofbraided UHMWPE yarn was sutured with MaxBraid™ 3-0 UHMWPE (availablefrom Teleflex, Limerick, Ireland), in an everted fashion using theBlalock stitch configuration.

Valves were implanted in adult sheep models (bread “swifter”, body mass65 kg) on the arrested heart under support of extra-corporealcirculation. Access to the aortic root was achieved through leftthoracotomy 3rd-4th i.c.s. The pulmonary artery was dissected and pulledaside to allow transverse incision of the aorta. Classical implant wasperformed under cardiac arrest using a running suture Prolene® 5-0. Theaorta was closed with a pericardial patch and the heart wasdefibrillated thereafter. The heart lung machine was disconnected.Echocardiography showed normal leaflet function without valvular orparavalvular regurgitation.

EXAMPLE 3

A valved conduit or valved graft was constructed from a single piece offlat sheet of chemically prepared porcine intestine submucosa(CorMatrix®, Roswell, US). In a series of chronic sheep and lamb, valveshaving a diameter 25 and 18 mm, respectively, were implanted as aninterponate graft between the outflow tract of the right ventricle andthe distal main pulmonic artery. The surgical access was the same asdescribed in Example 1 and implant was performed using extra-corporealcirculatory support. The pulmonic artery was cross sectioned above thepulmonic valve that was removed subsequently.

For a 25 mm diameter conduit/valve a trapezoid shaped sheet was preparedhaving one width of approximately 12 cm (A) and one of 14 cm (B) andhaving two sides (C and D) with lengths greater than 10 cm. From theflat sheet a conical tube was constructed by suturing together the freeslant sides C and D with a festooning 4-0 Prolene® suture in an evertedway. Excess material was cut away and the tube was folded and invertedin such way that the tubular part with larger circular edge B becamepositioned within the tube with circular edge A (outflow side) andleaving a folded rim at the inflow side. The circular edge B, formingthe free margin of the leaflets was divided in three parts having thesame length and subsequently fixed with a pledget armed suture (Prolene4-0) to the outer tube at 120° each. Herewith, three commissures of 3-4mm in the longitudal direction of the valve were created, and the threeindividual leaflets having excess length in their free margins coaptedwith at least 7 mm coaptation height without load. At the outflow sideof A a cuff remained, which was used to connect the valve duringimplantation to the transected pulmonic artery. The inflow side of thetube having the folded rim was connected to the pulmonic artery stump.Once implanted, echocardiography showed normal leaflet function withoutvalvular incompetence apart from some occasional minimal regurgitationin the centre of the valve.

Any one of the embodiments, aspects and preferred features or ranges asdisclosed in this application and relating to a method of making aprosthetic valve or a valve as obtained with the method may be combinedin any combination, unless otherwise stated herein or if technicallyclearly not feasible to a skilled person. The invention is furthersummarized in the below set of embodiments.

A prosthetic valve (400) comprising a leaflet assembly having at leastone leaflet (3) attached to a supporting element (2), which leaflet hasa free margin (5) that can move between a first position wherein thefree margin is flexed away from a closure surface (700) to allow bodyfluid to flow through the valve, and a second position wherein the freemargin abuts the closure surface to close the valve, and wherein theleaflet, without pulsatile load on the valve, can form a coaptationheight of more than 0.1 mm along the length of the free margin.

The prosthetic valve according to previous embodiment, wherein thecoaptation height is between 1 and 15 mm, preferably between 3 and 10mm, more preferably between 5 and 7 mm.

The prosthetic valve according to previous embodiments, wherein theleaflet has a geometry comprising a convex surface with a radius ofcurvature at the centre line of the leaflet of 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 mm.

The prosthetic valve according to previous embodiment, wherein theradius of curvature is between 1 and 20 mm, preferably about 12 mm.

The prosthetic valve according to any one of previous embodiments,wherein the leaflet has a geometry comprising a convex surface, andhaving a curvature height, the largest orthogonal distance between thecentre line and a straight line connecting the free margin at the centreof the valve and the nadir, of more than 1 mm, preferably more than 2,3, or 4 mm and at most 15, 14, 13, 12, 11 or 10 mm, and most preferablyof about 5 mm.

The prosthetic valve according to any one of the previous embodiments,wherein the free margin of the leaflet has excess length relative to thetheoretical length needed for closing the valve, preferably the excesslength is at least 7%, preferably between 10% and 40%, or between 15%and 30%.

The prosthetic valve according to any one of previous embodiments,wherein the leaflet is attach to the supporting element along acommissure that runs in parallel with the longitudinal axis of the valvestarting at the free margin, preferably the commissure has a length ofat least 1 mm and at most 9 mm, preferably 1-6 mm.

The prosthetic valve according any one of previous embodiments, whereinthe leaflet comprises an elastic sheet material having an elongation atbreak of 10% or less, preferably less than 9, 8, 7, 6, 5, 4, 3, 2 oreven 1%.

The prosthetic valve according to any one of previous embodiments,wherein the leaflet comprises a textile structure comprising one or moreelastic yarns having an elongation at break of 10% or less, preferablyof less than 9, 8, 7, 6, or 5%, more preferably of between 1 and 5%.

The prosthetic valve according to previous embodiment, wherein thetextile structure is a woven fabric made from the one or more elasticyarns, and preferably the woven fabric comprises plain, twill or basketweave patterns.

The prosthetic valve according to previous embodiment, wherein thetextile structure is a single piece of woven fabric, preferably a singlepiece of woven fabric comprising multiple stacked layers.

The prosthetic valve according to previous embodiments, wherein the freemargin of the leaflet is a selvedge of the woven fabric. The prostheticvalve according to previous embodiments, wherein the textile structureis a multilayer woven fabric comprising stacked layers, which layers areinterconnected, preferably by crossing warp or fill threads, at desiredlocations to define leaflets and supporting elements.

The prosthetic valve according to previous embodiments, wherein thewoven fabric is a two-layer fabric that comprises two selvedges at anopen side, and a continuous fold line at the opposite closed side.

The prosthetic valve according to previous embodiments, wherein thewoven textile structure is a seamless tubular fabric, optionally amulti-channel or multi-layer tubular fabric.

The prosthetic valve according to previous embodiments, made bycontinuously weaving the textile structure, subsequently cutting theresulting structure into desired lengths, and optionally stabilising thecut edges.

The prosthetic valve according to previous embodiments, wherein theelastic yarn has a linear density of less than 120 dtex, preferably alinear density of less than 60 dtex, preferably between 5 and 30 dtex,more preferably between 7 and 15 dtex.

The prosthetic valve according to previous embodiments, wherein thethickness of a layer of the textile structure, preferably a wovenfabric, is 20-200 μm, preferably between 40 to 150 μm, or between 50 to100 μm.

The prosthetic valve according to previous embodiments, wherein thetextile structure comprises polymeric filaments, preferably UHMWPEfilaments, more preferably the textile structure comprises at least 80mass % of UHMWPE filaments with a tenacity of at least 20 cN/dtex, morepreferably the warp and the fill yarn consist essentially of UHMWPEfilaments.

The prosthetic valve according to any one of previous embodiments,further comprising a stent (40) connected to the leaflet assembly.

The prosthetic valve according to previous embodiment, wherein the stentis connected by stitches, preferably by stitches made with a suture thathas similar strength as a yarn in the leaflet assembly, more preferablyby stitches made with the same type of yarn, or a by suture madetherefrom.

The prosthetic valve according to any one of previous embodiments,wherein the valve comprises two leaflets, the second leaflet acting asthe closure surface for the first leaflet and vice versa.

The prosthetic valve according to previous embodiment, wherein the valvecomprises three leaflets, each leaflet acting as the closure surface forthe other two leaflets.

The prosthetic valve according to any one of previous embodiments, beingan implantable prosthetic heart valve.

A leaflet assembly for a prosthetic valve as described in any one ofprevious embodiments.

A method of making a prosthetic valve (400), the valve comprising a atleast one leaflet (3) attached to a supporting element (2), whichleaflet has a free margin (5) that can move between a first positionwherein the free margin is flexed away from a closure surface (700) ofthe valve to allow a body fluid to flow through the valve, and a secondposition wherein the free margin abuts the closure surface to close thevalve, the method comprising:

-   -   providing a sheet material,    -   forming a leaflet assembly comprising at least one leaflet and a        supporting element from the sheet material, and    -   forming the valve therewith,        wherein forming the leaflet assembly comprises shaping the        leaflet to impose a geometry wherein the leaflet, without        pulsatile load on the valve, can form a coaptation height of        more than 0.1 mm along the length of the free margin.

The method according to previous embodiment, wherein the coaptationheight is at least 2, 3, 4 or 5 mm and at most 15, 13, 11, 10, 9, 8, or7 mm.

The method according to previous embodiment, wherein the coaptationheight is between 1 and 15 mm, preferably between 3 and 10 mm, morepreferably between 5 and 7 mm.

The method according to any one of previous embodiments, wherein thegeometry comprises a convex surface that has a radius of curvature atthe centre line of the leaflet of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 or 20 mm.

The method according to previous embodiment, wherein the radius ofcurvature is between 1 and 20 mm, preferably about 12 mm.

The method according to any one of previous embodiments, wherein thegeometry comprises a convex surface, with a curvature height of morethan 1 mm, preferably more than 2, 3, or 4 mm and at most 15, 14, 13,12, 11 or 10 mm, and most preferably of about 5 mm.

The method according to any one of previous embodiments, wherein theleaflet is formed such that the free margin of the leaflet has excesslength relative to the theoretical length needed for closing the valve,preferably the excess length is at least 7%, preferably between 10% and40%, or between 15% and 30%.

The method according to previous embodiment, wherein the excess lengthis created by one or more of the method steps chosen from the group ofpreforming the sheet material as having a specific shape, for example byforming a trapezium-like sheet material or a tapered or conical tubularmaterial, reducing the outer circumference of the valve, and shiftingthe leaflet surface before fixing the leaflet in the valve.

The method according to any one of previous embodiments, wherein theleaflet is attached to the supporting element along a commissure thatruns in parallel with the longitudinal axis of the valve starting at thefree margin, preferably the commissure has a length of at least 1 mm andat most 9 mm, preferably about 1-6 mm.

The method according to any one of previous embodiments, wherein thesheet material is an elastic material having an elongation at break of10% or less, preferably less than 9, 8, 7, 6, 5, 4, 3, 2 or even 1%.

The method according to any one of previous embodiments, wherein thesheet material is a textile structure comprising one or more elasticyarns having an elongation at break of 10% or less, preferably of lessthan 9, 8, 7, 6, or 5%, more preferably of between 1 and 5%.

The method according to previous embodiment, wherein the textilestructure is a structure woven from the one or more elastic yarns, andpreferably the woven fabric comprises plain, twill or basket weavepatterns.

The method according to previous embodiment, characterised in that thetextile structure is a single woven structure, preferably a wovenstructure comprising multiple stacked layers.

The method according to previous embodiments, wherein the free margin ofthe leaflet is woven as a selvedge.

The method according to previous embodiments, wherein the textilestructure is woven as a multilayer structure comprising stacked layers,which layers are interconnected, preferably by crossing warp or fillthreads, at desired locations to define leaflets and supportingelements.

The method according to previous embodiments, wherein the textilestructure is made by a double weaving process resulting in a two-layerfabric that has two selvedges at its open side, and a continuous foldline at the opposite closed side.

The method according to previous embodiments, wherein the textilestructure is made by a double weaving process resulting in a seamlesstubular fabric, optionally a multi-channel or multi-layer tubularfabric.

The method according to previous embodiments, comprising continuouslyweaving the textile structure, cutting the resulting structuresubsequently into desired lengths, and optionally stabilising the cutedges.

The method according to previous embodiments, wherein the elastic yarnhas a linear density of less than 120 dtex, preferably a linear densityof less than 60 dtex, preferably between 5 and 30 dtex, more preferablybetween 7 and 15 dtex.

The method according to previous embodiments, wherein the thickness of alayer of the textile structure, preferably a woven fabric, is 20-200 μm,preferably between 40 to 150 μm, or between 50 to 100 μm

The method according to previous embodiments, wherein the textilestructure comprises polymeric filaments, preferably UHMWPE filaments,more preferably the textile structure comprises at least 80 wt-% ofUHMWPE filaments with a tenacity of at least 20 cN/dtex, more preferablythe warp and/or the fill yarn consist of UHMWPE filaments.

The method according to any one of previous embodiments, furthercomprising connecting the leaflet assembly to a stent (40).

The method according to previous embodiment, wherein connecting is doneby applying stitches, preferably by using a suture that has similarstrength as the yarn in the leaflet assembly, more preferably by usingthe same type of yarn, or a suture made therefrom.

The method according to any one of previous embodiments, wherein thevalve comprises two leaflets, the second leaflet acting as the closuresurface for the first leaflet and vice versa.

A method according to any one of the previous embodiments, wherein thevalve comprises three leaflets, each leaflet acting as the closuresurface for the other two leaflets.

A method for making a leaflet assembly for a prosthetic valve asdescribed in any one of previous embodiments.

A leaflet assembly or a prosthetic valve as obtainable by the methodaccording to any one of previous embodiments.

1. A prosthetic heart valve that can take a first form wherein the valveis open and a second form wherein the valve is closed, the valvecomprising a leaflet assembly having three leaflets attached to asupporting element at respective first and second commissures, theleaflets having a free margin that can move between a first positionwherein the valve takes the first form and a second position wherein thevalve takes the second form with each leaflet acting as a closuresurface for the other leaflets, wherein the leaflets can form acoaptation height of between 1 and 15 mm along the free margin without apulsatile load on the valve and without requiring substantial extensionof the leaflets.
 2. The prosthetic valve according to claim 1, whereinthe coaptation height is between 3 and 10 mm.
 3. The prosthetic valveaccording to claim 1, wherein the coaptation height is between 5 and 7mm
 4. The prosthetic valve according to claim 1, wherein the leafletscomprise an elastic sheet material having an elongation at break of 10%or less.
 5. The prosthetic valve according to claim 1, wherein theleaflets comprise an elastic sheet material having an elongation atbreak of less than 6%.
 6. The prosthetic valve according to claim 4,wherein elongation of the sheet material during use in the valve is lessthan 5%.
 7. The prosthetic valve according to claim 4, wherein theleaflets comprise a textile structure comprising at least one elasticyarn having an elongation at break of 10% or less.
 8. The prostheticvalve according to claim 7, wherein the textile structure is made byknitting, braiding or weaving the one or more elastic yarns.
 9. Theprosthetic valve according to claim 7, wherein the textile structure isa woven fabric made from the elastic yarn.
 10. The prosthetic valveaccording to claim 9, wherein the woven fabric comprises plain, twill orbasket weave patterns.
 11. The prosthetic valve according to claim 9,wherein the free margins of the leaflets are a selvedge of the wovenfabric.
 12. The prosthetic valve according to claim 7, wherein theelastic yarn has a linear density of 5-120 dtex.
 13. The prostheticvalve according to claim 7, wherein the elastic yarn has a lineardensity of at least 7-30 dtex.
 14. The prosthetic valve according toclaim 7, wherein the textile structure has a thickness of 20-200 μm. 15.The prosthetic valve according to claim 7, wherein the textile structurehas a thickness of 50-100 μm.
 16. The prosthetic valve according toclaim 7, wherein the textile structure comprises UHMWPE filaments. 17.The prosthetic valve according to claim 7, wherein the textile structureis a woven fabric with warp and yarns consisting essentially of UHMWPEfilaments.
 18. The prosthetic valve according to claim 1, wherein thefree margins have a length extending between first and secondcommissures, which length is at least 7% in excess relative to atheoretical length needed for closing the valve.
 19. The prostheticvalve according to claim 1, wherein each leaflet is attached to thesupporting element along commissures that run in parallel with thelongitudinal axis of the valve starting at the free margin, thecommissures having a length of at least 1 mm.
 20. The prosthetic valveaccording to claim 1, further comprising a stent connected to theleaflet assembly.
 21. A method of making the prosthetic valve accordingto claim 1 comprising: (i) providing a sheet material, (ii) forming aleaflet assembly comprising three leaflets and a supporting element fromthe sheet material, and (iii) forming the valve therewith, whereinforming the leaflet assembly according to step (ii) comprises shapingthe leaflets to impose a geometry wherein the leaflets without pulsatileload on the valve and without requiring extension of the leaflets canform a coaptation height of between 1 and 15 mm along the free margin.22. The method according to claim 21, wherein step (iii) comprisesconnecting the leaflet assembly to a stent.